白袍恐懼症

Bladder cancer

1.      Introduction

90%屬於TCC

2.      Clinical

(1). painless hematuria: unexplained hematuria in individuals >40 years requires evaluation for a possible malignancy), gross hematuria10~20%, microscopic hematuria2~5%為Bladder cancer

Typically intermittent, gross, painless, and present throughout micturition

由hematuria出現的時間，簡單區分位置：

-beginning of urination -> urethral source

-between voidings, or as a stain on undergarments, while the voided urine itself appears clear -> origin at the urethral meatus or the anterior urethra

-terminal hematuria -> bladder neck or prostatic urethra

-throughout voiding can originate from anywhere in the urinary tract including the bladder, ureters, or kidneys 

(2). Pain: the result of locally advanced or metastatic tumor, related to the size and location of the primary tumor or its metastases

- Flank pain: tumor obstructs the ureter at any level. The pain is similar to that experienced with the passage of urinary stones, and may or may not be associated with hematuria.

-Suprapubic pain: a sign of a locally advanced tumor that is either directly invading the perivesical soft tissues and nerves, or obstructing the bladder outlet and causing urinary retention.

- Hypogastric and perineal pain: signs of disease invading the obturator fossa, presacral nerves, or the urogenital diaphragm.

- Abdominal or right upper quadrant pain: abdominal lymph node or liver metastases

- Bone pain: bone metastases

- Significant and persistent headache or disordered cognitive function: presence of intracranial metastases

(3). Voiding symptoms

- Irritative voiding symptoms occur in approximately one-third of patients. The complex of dysuria, frequency, and urgency in particular is highly suggestive of bladder CIS.

-Obstructive voiding symptoms are less common and may be due to tumor location at the bladder neck or prostatic urethra. Symptoms include straining, an intermittent stream, nocturia, decreased force of stream, and a feeling of incomplete voiding. On occasion, gross hematuria may result in "clot retention".

(4). Constitutional symptoms: fatigue, weight loss, anorexia, and failure to thrive are usually signs of advanced or metastatic disease and denote a poor prognosis.

3.      Risk factor

Tobacco，saccharin (糖精)，cyclophosphamide，另外，反覆的cystitis和TURBT (經尿道膀胱腫瘤切除術)對epithelium的傷害都可能和膀胱癌有關。

4.      Diagnosis

Cytoscopy: golden standard, assess whether or not muscle invasion is present, and provide initial therapy for non-muscle-invasive lesions 

Cytology細胞學檢查：

High specificity (90%)，low sensitivity (40-60%)

適合幫助診斷high grade lesions、CIS、以及影像上不顯著的urinary tract tumor

缺點：會因判讀者不同而造成不一樣的結果

5.      Grading

6.      staging (TNM system，另外還有Marshall-Jewtt system)

-Superficial type: not invade the muscular bladder wall=> treat with transurethral resection, 65~85% patients will cure.

-Invasive type:

TX: Primary tumor cannot be assessed

T0: No evidence of primary tumor

Ta: Noninvasive papillary carcinoma(只有mucosa被侵犯)

Tis(Carcinoma in situ): "flat tumor"

T1: Tumor invades subepithelial connective tissue

T2: Tumor invades muscularis propria

  pT2a: Tumor invades superficial muscularis propria (inner half)

  pT2b: Tumor invades deep muscularis propria (outer half)

T3: Tumor invades perivesical tissue(involve 至organ之外)

  pT3a  Microscopically

  pT3b  Macroscopically (extravesical mass)

T4: Tumor invades any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall

  T4a  Tumor invades prostatic stroma, uterus, vagina

  T4b  Tumor invades pelvic wall, abdominal wall

7.      prognosis factor

T stage

Tumor grade：越高預後越差

Multiplicity of tumors：多發腫瘤較單一腫瘤為差

Tumor size：size越大，預後越差

Previous recurrence rate：是否有復發？ (70%的bladder cancer會復發)

8.      treatment

(1). Primary tumors without muscle invasion (Ta and T1 lesions) -> TURBT (Transurethral resection of bladder tumour)

(2). significant risk of recurrence and/or progression -> intravesical therapy

(3). high-risk disease features (high-grade, T1, or Tis) -> a course of intravesical BCG immunotherapy following a restaging TURBT

For patients given intravesical BCG immunotherapy:

- the initial course consists of six weekly doses of BCG

- maintenance BCG therapy at least one year if possible

- should not be administered to patients with traumatic catheterization, active cystitis, or persistent gross hematuria following TURBT.

Adjuvant Intravesical Chemotherapy (適用於T1以下的膀胱癌)

從膀胱內灌注化療藥物的好處：

-預防或延後tumor的recurrence

-根除剩餘無法切除的tumor

-預防tumor progression (但是目前大部分的paper都不支持這一點)

-既然可以預防或延後tumor的recurrence，膀胱切除的手術也可以減少

-維持生活品質

-從膀胱注入的藥物：Alkylating、Anthracyclines (小紅莓)、Biological response modifiers (如BCG immunotherapy、interferon、interleukins)。

BCG immunotherapy的作用機制是透過immunopotentiation，就是刺激免疫細胞的活性使免疫細胞能夠辨識腫瘤，促使immune response對抗癌細胞(產生inflammation而不會infection，無致病能力)。

(4). muscle-invasive (T2)=> radical cystectomy + urinary diversion (尿路分流重建) + 雙側的pelvic lymph nodes切除=> combined modality:

preoperative (neoadjuvant) cisplatin-based combination chemotherapy rather than cystectomy alone

(5). highly active in patients with metastatic disease: MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin)

utility of adjuvant chemotherapy remains highly controversial, but no level 1 data currently exist to support its routine use